Réaction #8595

Équation de réaction

water

triethylamine

2-(6-chloro-2-pyridinyl)-1-(methoxyphenyl)ethanone oxime

trifluoroacetic anhydride

→

7-chloro-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridine

Rendement 52.0%

Solvants

1,2-dimethoxyethane

1,2-dimethoxyethane

Conditions de réaction

Traitement

1. 1
   Autrethe temperature below 10° C.
2. 2
   workup.ADDITIONduring the addition
3. 3
   workup.ADDITIONAfter the addition
4. 4
   TempératureThe solution was then cooled to 4° C.
5. 5
   Températureto warm to room temperature
6. 6
   Températurethe reaction was heated at 75° C. for 15 hours
7. 7
   ExtractionThe resulting suspension was extracted with ethyl acetate
8. 8
   SéchageThe organic phase was dried (magnesium sulfate)
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated to a solid
11. 11
    AutreThis solid was recrystallized from methanol

Mode opératoire

To a solution of 2-(6-chloro-2-pyridinyl)-1-(methoxyphenyl)ethanone oxime (38.7 g, 140 mmol) in 1,2-dimethoxyethane (156 mL) at 0° C. was added trifluoroacetic anhydride (20 mL, 140 mmol), keeping the temperature below 10° C. during the addition. After the addition was complete, the reaction was warmed to 15° C. The solution was then cooled to 4° C. and a solution of triethylamine (39 mL, 280 mmol) in 1,2-dimethoxyethane (15 mL) was added over a period of 0.5 hours. The mixture was allowed to warm to room temperature and was stirred at room temperature for 1.5 hours. To this mixture was added iron(II) chloride (0.18 g, 1.4 mmol) and the reaction was heated at 75° C. for 15 hours. The reaction mixture was poured into water (300 mL). The resulting suspension was extracted with ethyl acetate. The organic phase was dried (magnesium sulfate), filtered and concentrated to a solid. This solid was recrystallized from methanol to give 7-chloro-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridine (18.7 g, 52%) as pale yellow needles. 1H NMR (CDCl3): δ 7.91 (d, 2H), 7.43 (d, 1H), 7.01 (t,1H), 6.95 (d, 2H). 6.81 (d,1 1H), 6.80 (s, 1H), 3.83 (s, 3 H); MS m/z 259 (M+1).

Source